Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15120%2F19%3A73594913" target="_blank" >RIV/61989592:15120/19:73594913 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/carcin/article/40/3/432/5259175" target="_blank" >https://academic.oup.com/carcin/article/40/3/432/5259175</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/carcin/bgy187" target="_blank" >10.1093/carcin/bgy187</a>
Alternative languages
Result language
angličtina
Original language name
Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci
Original language description
DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 x 10(-7)) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 x 10(-6)) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 x 10(-4)). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30204 - Oncology
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Carcinogenesis
ISSN
0143-3334
e-ISSN
—
Volume of the periodical
40
Issue of the periodical within the volume
3
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
432-440
UT code for WoS article
000472794100005
EID of the result in the Scopus database
2-s2.0-85066163672